The objects of the proposed research are to utilize immunological autoradiographic, electrophysiological, and direct receptor binding methods to study some of the pharmacologic activity of narcotic analgesics. Derivatives of morphine and other opioids have been prepared and chemically characterized. Using the ammonium sulfate technique the stereochemical requirements of the antibody binding sites are being evaluated by determining the capacity of these various unlabeled compounds to inhibit the binding of the opioid used for immunization. Once the chemical nature of the structures that are bound by the antibody binding sites are determined, the antibodies will be reacted with biologically active, enzymatically stable enkephalin analogs to determine if they can inhibit binding of the radiolabeled immunizing opioid. Such capacity could suggest some similarity in the spacial configurations of enkephalin and opioids. Antibodies against meperidine have been used to study placental transfer to meperidine and these studies are now being completed. The concentrations of meperidine in the cord serums of infants have been correlated with the extent of observed perinatal depression and these antibodies are further being evaluated as highly specific reagents for assay methods to detect individual opioids and possibly distinguish between the opioids and their metabolic products. Anti-opioid antisera are also being used to investigate the pharmacologic mechanism of opioid action, for determining affinity constants of tissue receptors and for studying the effects of antibodies on the biologic activities of opioids using inhibition of the electrically induced contractions of the guinea pig ileum. Experiments have been initiated which are designed to study the localization of opioids in the myenteric plexus of the guinea pig ileum. Morphologic localization studies are being carried out employing autoradiography and this data will be correlated with electrophysiological measurements of ileal contractility and opioid receptor binding assays in the same tissue. BIBLIOGRAPHIC REFERENCE: Wainer, B.H., Wung, W.E., Hill, J.H., Fitch, F.W., Fried, J., and Rothberg, R.M.: The production and characterization of antibodies reactive with meperidine. J. Pharmacol. Exp. Ther. 197:153, 1976.